Transcript Parkinson's Disease: Epidemiology, Etiology, and Pathogenesis

PSYCHIATRIC ASPECTS of
PARKINSON’S DISEASE
and Related Disorders
Michael J Kelly MD FRCPC
Grand River Hospital
Kitchener-Waterloo
7 May 2008
Learning Objectives
 Recognize the psychiatric co-morbidities
associated with Parkinson’s Disease and
related disorders
 Better appreciate management of the
common neuropsychiatric complications
Impact
• The impact of PD on individuals is a wideranging as the clinical manifestations of the
disease itself
• The disease can make even the most
mundane daily activity a challenge
• Most discussion of PD focuses on its motor
features, such as tremor, slowness, and
imbalance
• Yet the so-called “non-motor”
aspects of the illness, depression,
anxiety, memory difficulties, sleep
disturbances, etc., are often
prominent and can cause as much
or more difficulty for individuals
struggling with the disease
James Parkinson 1817
• “ a more melancholy
object I never beheld”
Meds: Friend or Foe?
• Pharmacologic issues regarding appropriate
management of the neuropsychiatric
aspects are particularly complex
• Some of the medications used to treat PD
aggravate neuropsychiatric symptoms
• Agents used to control behavioural
disturbances in PD may increase
parkinsonism
Treatment
Maintain motion
Control emotion
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“Motion-Emotion Conundrum”
Behavioural
• Behavioural and neuropsychiatric aspects of
PD represent important clinical challenge in
optimizing the quality of life of patients and
their caregivers.
• Frequently accounts for a substantial portion
of the distress associated with the disease,
the burden experienced by caregivers, the
requirement for institutionalization or
nursing home placement.
Associated Psychiatric Features
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Depression
Anxiety
Apathy/abulia
Affective lability (nonmotor fluctuations)
Disinhibtion, mania, gambling, hypersexuality
Agitation
Aggression
Confusion/disorganization/dementia
Delirium
Caregiver strain!
FREQUENCY OF
NEUROPSYCHIATRIC SYMPTOMS
SYMPTOM
Anxiety
Fatigue
Irritability
Hallucinations
Self-withdrawal
Euphoria
Lassitude/weariness
Sadness
Witjas T et al. Neurology, 2002;59:408-413.
FREQUENCY
%
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RISK FACTORS FOR
NON-MOTOR COMPLICATIONS
• Early age of disease onset
• Longer duration of disease
• Higher doses of levodopa
• Age of patient
• Presence of motor fluctuations
Preclinical Parkinson’s Disease
• No specific clinical markers known
• 4-13% of autopsies in elderly showing
incidental Lewy bodies are regarded as
preclinical cases
• Increased risk of neuroleptic parkinsonism
• Duration of preclinical phase unknown
(several years to several decades?)
• PET studies may identify preclinical cases
www.wemove.org
DEPRESSION IN
PARKINSON’S DISEASE
•Affects 40-50% of patients
•Characterized by:
Feeling of guilt
Lack of self esteem
Loss of initiative
Helplessness, remorse, sadness
•Causes may be endogenous, exogenous,
or both
Key Features of Depression in
PD
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Reported dysphoria/sadness
Apparent sadness
Anhedonia
Exaggerated pessimism
Suicidal ideation
Irritability
Comorbid anxiety
Diagnostic Difficulties
• Underdiagnosis:
• Overdiagnosis; PD
interpreted as depression - Bradykinesia, masked
facies mask depression
- Rigidity
Cognitive
impairment
- Masked facies
- Bradyphrenia
- Bradykinesia
- Low voice
- Bradyphrenia
- Ageism
- Cognitive impairment
- Lack of attention to
- Insomnia
emtional problems
- Apathy
Potential Mechanisms
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Psychosocial stress in general
Genes
Comorbidity
Structural and functional brain changes
Antiparkinson agents
Latent psychiatric disease
Psychological reaction to diagnosis and
impairment
Antidepressant, Dopamine, and
EPS
• SSRI may induce/worsen parkinsonism
• 5HT/NA agents more effective than SSRI?
• ECT increases dopaminergic activity and may
improve depression + parkinsonism*
• Methylphenidate improves depression and
apathy in PD?
• Pramipexole improves depression and apathy in
PD?
Psychosis in Parkinson’s Disease
(PD)
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Major clinical challenge
Major source of caregiver burden
#1 factor in nursing home placement
Associated with increased mortality
Prognosis improved with advent of atypical
antipsychotics
Prevalence of Psychosis
• ~8%-40% reported rates
• Depends on definition of psychosis,
Parkinson’s disease (PD), congnitive
impairment
• ~5%-17% without significant dementia
• ~42%-81% with significant dementia
General Categories of Psychosis
• Features
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Vivid dreams/nightmares, disorientation, hallucinations,
delusional thought
-Visual hallucinations with insight
“Benign” psychosis
• Hallucinations and/or delusions without
insight
• Hallucinations and/or delusions with
delirium
Delusions
• ~3%-30% reported prevalence rates
• Phenomena
-Delusions of spousal infidelity
Phantom border
- Feature of affective psychosis
- Often accompany hallucinations
- Other persecutory delusions
Etiology/Risk Factors for Psychosis
• No single explanation
• Most commonly reported cause
- Dopaminergic medications
 Rare cases before L-dopa
 All dopamine agents can elicit psychosis
 Reduction in dopamine medications decrease psychosis
Treatment of Psychosis
• Step 1: Primary prevention
• Step2: Treat medical illnesses
• Step 3: Eliminate psychoactive
medication
- Benzodiazepines, opiates, H2
Blockers,
tricyclic anitpdepressants (TCAs),
antispasmodics
• Step 4: Treat comorbid pscyhiatric
illnesses
Treatment of Psychosis
• Step 5: Nonpharmacological strategies
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- Education, reassurance,
activity/day programs, placement
• Step 6: Eliminate antiparkinsonian
medications
• Step 7: Address disrupted sleep
• Step 8: Trial of cholinesterase inhibitors
• Step 9: Trial of neuroleptic agents
Quetiapine
Most common first-line agent
6.25-12.5 mg starting dose
Escalate as needed/tolerated
Adverse effects
- Sedation
- Orthostasis
- Confusion
- Increased parkinsonism, especially with dementia
- Increased fluctuations
Clozapine
Most effective agent for psychosis in PD, but use
avoided because of need for blood monitoring
Dose range: 6.25 mg od ≥ 200 mg/day
Starting dose 6.25 mg qhs
Escalate as needed/tolerated
Adverse effects
- Sedation
- Orthostasis
- Confusion
- Worse parkinsonism
- Agranulocytosis
- Seizures
Other Strategies to Treat
Psychosis
• Cholinesterase inhibitors
-Positive results in open-label studies of PD
and Lewy body dementia
- Variable tolerance- need to monitor
- May still benefit from lower doses
• Electroconvulsive Therapy (ECT)
- Especially with psychotic depression
Preventive Strategies
• Evaluate PD regimen for overmedication,
inadequate medication, fluctuations
• Address early
-Mood disorders
- Sleep disorders
 Adjust PD medications- 24 hour dopamine needs
 Trazodone, quetiapine
- Cognitive impairment
 Cholinesterase inhibitors
 ? Other Alzheimer’s disease treatments
Sexual Desire and Function
• Individual variation in effect of PD
• Some patients have hypersexuality with
dopaminergic drugs(Impulse Control Disorders
• Erectile dysfunction
• Other causes of sexual dysfunction
– depression
– SSRIs
– endocrine dysfunction
www.wemove.org
Impulse Control Disorders (ICDs) in PD
Pathological Gambling
Hypersexuality
Pathological Shopping
Compulsive Eating
Dopaminergic Medication abuse
Punding
ICDs: General Treatment Strategoes
Adjust antiparkinsonian treatment
– Reduce dosage of dopaminergic medications
– Change to a different dopamine agonist
– Discontinue dopamine agonist
Pharmacologic trials- anecdotal
– Quetiapine and clozapine
– Antiandrogens, valproate, lithium, atomoxetine, treatment
of comorbid depression
Psychosocial supports
– Limit access to behaviours
– Counseling, psychotherapy, CBT, Gamblers Anonymous
SLEEP DISTURBANCES IN
PARKINSON’S DISEASE
•Insomnia
•REM behavior disorder
•Nightmares
•Obstructive sleep apnea
•Excessive daytime sleepiness
COGNITIVE IMPAIRMENT IN
PARKINSON’S DISEASE
• Affects up to 40% of patients
• Late feature of PD
• Differential diagnosis: PDD vs AD vs
DLB
• Frontal-executive dysfunction,
impairments of visuo-spatial abilities,
temporal ordering, memory and attention
• Increases caregiver burden
PD with Dementia
DSM-IV
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Memory impairment
+ 1 or more of praxis,
executive functions(
planning, abstraction,
conceptualization,
reasoning ) ,gnosis
Decline, impair
occupational/social fn
Not delirium
Consequence of
Parkinson’s disease
• Cummings and
Benson
• 3/5 domains
• Language
• Memory
• Complex cognition
( executive functions)
• Visuospatial functions
• Personality or emotion
Neurodegenerative Disorders with
Parkinsonism (I)
• Diffuse Lewy body disease
– Early onset of dementia
– Delusions and hallucinations
– Agitation
www.wemove.org
DLB
• Fluctuating cognition
( attention / arousal / alertness )
• Recurrent visual hallucinations
• Motor features of parkinsonism
• Ofen with repeated falls, syncope, transient loss
of conciousness
• Neuroleptic sensitivity, delusions, other
hallucinations
DLB vs PDD
• Arbitrary “ one year rule “
• DLB- dementia syndrome must occur before or
within one year of onset of parkinsonism
• PDD-dementia syndrome evident more than one
year after onset of parkinsonism ( actually often
occurs as a later stage complication, at least 8-10
years after motor symptoms.)
• Cumulative prevalence of dementia 80% in PD
pts with 10+ yrs of motor symptoms
DLB vs PDD
2/3 pts with DLB have parkinsonism
In DLB, < resting tremor, <asymmetry and
>rigidity, postural and gait impairment
• In autopsy-proven cases, one of myoclonus,
absence of rest tremor, no response to levodopa,
or no perceived need to treat with levodopa,
was10X more likely to represent dx of DLB
than PDD
Neurodegenerative disorders with Parkinsonism
• Progressive supranuclear palsy
– Supranuclear downgaze palsy, (difficulty
looking down )
– Upright posture ,broad-based and stiff gait
postural instability /frequent falls
– Axial rigidity, nuchal dystonia ( neck in
extension )
www.wemove.org
Neurodegenerative disorders with Parkinsonism
• Progressive supranuclear palsy
– Pseudobulbar emotionality/ emotional
incontinence
– -Furrowed brow/stare
– Dementia
– - poor response to levodopa
www.wemove.org
Neurodegenerative disorders with
Parkinsonism (II)
• Corticobasal degeneration
– Unilateral akinesia and rigidity, coarse tremor
,unresponsive to levodopa
– Limb apraxia/
limb dystonia
– alien limb
– myoclonus
www.wemove.org
Neurodegenerative disorders with
Parkinsonism (III)
• Multiple system atrophy
– Shy-Drager syndrome
• Autonomic insufficiency—orthostasis,
impotence
– Striatonigral degeneration
• Tremor less prominent
– Olivopontocerebellar atrophy
• Cerebellar signs
www.wemove.org
Neurodegenerative Disorders with
Parkinsonism (IV)
• Alzheimer’s disease
– Dementia is the primary clinical
syndrome
– Rest tremor is rare
www.wemove.org
Differential Diagnosis of PD:
Hereditary disorders associated
with parkinsonism:
– Wilson’s disease
– Huntington’s disease
– Dentatorubro-pallidoluysian atrophy
(DRPLA)
– Machado-Joseph disease (SCA-3)
www.wemove.org
Differential Diagnosis of PD:
Secondary Parkinsonism
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Drug-induced
Toxin-induced
Metabolic
Structural lesions (vascular parkinsonism,
etc.)
• Hydrocephalus
• Infections
www.wemove.org
Clues Suggesting Atypical Parkinsonism
• Early onset of, or rapidly progressing,
dementia
• Rapidly progressive course
• Supranuclear gaze palsy
• Upper motor neuron signs
• Cerebellar signs—dysmetria, ataxia
• Urinary incontinence
• Early symptomatic postural hypotension
www.wemove.org
TREATMENT OF
COGNITIVE IMPAIRMENT
IN PARKINSON’S DISEASE
•Cholinesterase inhibitor
•Avoid offending medications
•Symptomatic behavioral treatment
•Caregiver education
Altered Mental States NYD
• Confusion, sedation, dizziness, hallucinations,
delusions
• Reduce or eliminate CNS-active drugs of lesser
priority
– anticholinergics
– amantadine
– hypnotics
– sedatives
– muscle relaxants
– urinary spasmodics
• Reduce dosage of DA, COMT inhibitor, or LD
www.wemove.org
Treatment
• Order for elimination of PD meds
-Anticholinergics
- Selegiline
- Amantadine
- Dopamine agonists
- COMT inhibitors
- Levodopa
TREATMENT OF NEUROPSYCHIATRIC
PROBLEMS IN PARKINSON’S DISEASE
•Reduce / discontinue medications
•Treat underlying medical illness
•Antidepressants
•Atypical neuroleptics
•Keep active / exercise
•Educate caregivers
•Psychological counseling
Where and When Do Geriatric Psychiatrists
See PD Patients ?
• Often involved with complex cases
- Associated behavioural disturbances
- Other psychiatric comorbities
- Other medical comorbities
• Multiple settings
- Impatient consultation-liaison
- Impatient psychiatry
- Nursing homes
- Freeport Neurobehaviour Unit
- Emergency room
References
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Menza M ,Marsh L
Psychiatric Issues in
Parkinson’s Disease
Taylor&Francis 2006
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Treatment of Psychiatric
Co-morbidities in
Patients with Parkinson’s
Disease
McDonald, W.H.,Chair
Symposium
AAGP March 2008
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Slides;
Houston Medical Center –
Parkinson’s Disease
Research, Education, and
Clinical Center
Slides;
WE MOVE Parkinson’s
Disease Teaching Slide Set
www.wemove.org